Effect of lentivirus-mediated RNA interference silencing IL-1 type Ⅰ receptor on signal transduction in a rat model of osteoarthritis
- VernacularTitle:慢病毒介导RNAi沉默IL-1 Ⅰ型受体在大鼠骨关节炎MAPK信号转导中的作用
- Author:
Bin ZHOU
;
Yonglin YU
;
Fengjian YANG
;
Huimin REN
- Publication Type:Journal Article
- Keywords:
osteoarthritis;
mitogen-activated protein kinase;
RNAi;
IL-1R Ⅰ;
gene therapy
- From:
Fudan University Journal of Medical Sciences
2009;36(4):379-383
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effects of lentivirus-mediated RNA interference silencing IL-1 type Ⅰ receptor on the expression of mitogen-activated protein kinase (MAPK) in a rat model of osteoarthritis (OA), and to explore the role of IL-1 and MAPK in OA. Methods Forty SD rats were randomly divided into four groups(A-D, each group: n = 10). The rats (A-C group) were underwent unilateral anterior cruciate ligament transaction and partial excision of the medial meniscus. At day 7 and 9 after operation, the rats of group A were respectively received 40 μL of lentivirus-mediated RNAi silencing IL-1 type Ⅰ receptor by intra-articular injection, while the rats of group B were received lentivirus-mediated RNAi non-silencing IL-1 type Ⅰ receptor, and the rats of group C were received saline. The rats of group D were taken for normal control. All rats were sacrificed four weeks after the surgery. The knees were harvested to observe macropathologic changes of the joint cartilage. ERK1/2, JNK1/2 and p38 proteins in the cartilage were detected by Western blot. Results Cartilage degradation in group A was milder than that in group B and C (P<0.05),but was worse compared to group D (P<0.05). Level of p38 expression in cartilage in group A was lower than that in group B and C (P<0. 05), but had no significant difference compared to group D (P>0.05). Levels of ERK1/2 and JNK1/2 expressions in cartilage in group A were lower than that in group B and C(P<0.05),but was significantly increased compared to group D(P<0.05). Conclusions Lentivirus-mediated RNAi silencing IL-1 type Ⅰ receptor can inhibit the expression of MAPK, in particular,p38 protein was strongly inhibited.
